Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy
The blood–retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal st...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1774 |
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| author | Aleksandra Agafonova Alessia Cosentino Ivana Roberta Romano Giovanni Giurdanella Floriana D’Angeli Rosario Giuffrida Debora Lo Furno Carmelina Daniela Anfuso Giuliana Mannino Gabriella Lupo |
| author_facet | Aleksandra Agafonova Alessia Cosentino Ivana Roberta Romano Giovanni Giurdanella Floriana D’Angeli Rosario Giuffrida Debora Lo Furno Carmelina Daniela Anfuso Giuliana Mannino Gabriella Lupo |
| author_sort | Aleksandra Agafonova |
| collection | DOAJ |
| description | The blood–retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A<sub>2</sub> activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs. The data obtained highlighted the potential of autologous differentiated ASCs in future clinical applications based on cell therapy to counteract the damage induced by DR. |
| first_indexed | 2024-03-08T03:55:08Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T03:55:08Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ea89af614c264a8389c6297de4e0475d2024-02-09T15:14:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253177410.3390/ijms25031774Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic RetinopathyAleksandra Agafonova0Alessia Cosentino1Ivana Roberta Romano2Giovanni Giurdanella3Floriana D’Angeli4Rosario Giuffrida5Debora Lo Furno6Carmelina Daniela Anfuso7Giuliana Mannino8Gabriella Lupo9Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyFaculty of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, ItalyDepartment of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, ItalyDepartment of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, ItalyThe blood–retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A<sub>2</sub> activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs. The data obtained highlighted the potential of autologous differentiated ASCs in future clinical applications based on cell therapy to counteract the damage induced by DR.https://www.mdpi.com/1422-0067/25/3/1774adipose mesenchymal stem cellspericyte-like differentiationhuman retinal endothelial cellsblood–retinal barrierdiabetic retinopathyhyperglycemia |
| spellingShingle | Aleksandra Agafonova Alessia Cosentino Ivana Roberta Romano Giovanni Giurdanella Floriana D’Angeli Rosario Giuffrida Debora Lo Furno Carmelina Daniela Anfuso Giuliana Mannino Gabriella Lupo Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy International Journal of Molecular Sciences adipose mesenchymal stem cells pericyte-like differentiation human retinal endothelial cells blood–retinal barrier diabetic retinopathy hyperglycemia |
| title | Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy |
| title_full | Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy |
| title_fullStr | Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy |
| title_full_unstemmed | Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy |
| title_short | Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy |
| title_sort | molecular mechanisms and therapeutic implications of human pericyte like adipose derived mesenchymal stem cells in an in vitro model of diabetic retinopathy |
| topic | adipose mesenchymal stem cells pericyte-like differentiation human retinal endothelial cells blood–retinal barrier diabetic retinopathy hyperglycemia |
| url | https://www.mdpi.com/1422-0067/25/3/1774 |
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